The objective of this proposal is to examine the role of the liver in gastrointestinal cancer immunity, in emphasizing its central role in the reticuloendothelial system. Efforts will be made to determine if phagocytosis of gastric cancer cell components including tumor-specific antigen fragments takes place in the liver. In order to develop a model similar to human gastrointestinal cancer, we will induce gastric cancers in inbred rats using nitrosoureas and pass these malignancies into tissue culture to allow quantitative immunological assays. Early passage cells will be viably frozen and stored in liquid nitrogen to preserve the original antigenic specificities so far as possible. An attempt will then be made to determine if Kupffer cells can be rendered cytotoxic to the gastric cancer cells. Kupffer cells will also be isolated and studied in vitro using a non-enzymatic isolation method. The overall goal of the investigation will be to determine whether in situ immune cytolysis of metastatic adenocarcinoma cells within the liver can be facilitated by immune sera. The model systems developed should also be useful in later studies on alternative techniques for the control of microscopic hepatic metastases at the time of surgery.